Package of sensitive articles

ABSTRACT

The invention is directed to the treating, e.g. sterilizing and packaging of medical devices and other articles, particularly such devices and articles which are reactive to oxygen or moisture containing atmospheres. The sterilized package has a container which includes at least one portion which is gas permeable and at least one portion which is gas impermeable and an interior in fluid communication with the gas permeable portion. The container may be sealed by applying an impermeable patch to the permeable portion thereof or by disposing the container in an enclosure formed of impermeable material and sealing the enclosure. After exposing the container to a sterilizing gas, the gas permeable portion may be removed or sealed off from the gas impermeable portion of the container in order to provide a package which is gas impermeable and can protect one or more articles within the interior of the container against environmental gases and moisture.

RELATED APPLICATIONS

This application is based upon and claims priority to ProvisionalApplication Ser. No. 60/537,972, filed on Jan. 20, 2004 and ProvisionalApplication Ser. No. 60/540,828, filed on Jan. 29, 2004. Bothapplications are incorporated herein by reference in their entireties.

BACKGROUND OF THE INVENTION

The present invention relates generally to sterilized medical devicesand packaging for sterilized medical devices. In particular, the presentinvention relates to the packaging of sterilized environmentallysensitive medical devices, such as drug-coated stents.

Most, if not all, disposable medical devices require sterilization priorto or concurrent with packaging. The packaging, which may be in the formof a pouch, bag, tube, box, or other sealed container, will maintain thesterility of the product until it is withdrawn from the packaging foruse. A particularly successful system and method for sterile packagingof medical devices relies on use of high-density polyethylene (HDPE)pouches which are used to contain the medical device or other product.The device may be placed in the package prior to sterilization.Sterilization is then effected by placing the package in an environmentincluding a sterilant gas, such as ethylene oxide (EtO), ethylene oxidewith nitrogen, various blends of ethylene oxide and carbon dioxide,ethylene oxide with chlorofluorocarbon diluent(s), Oxyfume 2000 seriesof sterilant, ozone, hydrogen peroxide, chlorine dioxide, or others. Thespun HDPE material, such as Tyvek® which is available from MedicalPackaging Division of E. I. DuPont de Nemours and Company (DuPont),permits passage of the small molecule sterilant gas while remaining abarrier to bacteria, viruses, and other larger substances which mightcompromise sterility. It also acts as a barrier to water and otherfluids which might detrimentally affect the sterilized contents.

While this packaging system has been highly successful for conventionalmedical devices, such as catheters, stents, surgical instruments,probes, and the like, it is frequently not suitable for “hybrid” deviceswhich contain coatings or components which are subject to oxygendegradation. For example, the use of drug-eluting stents is promising torevolutionize interventional cardiology. The stents are coated with drugat a central fabrication facility and must be distributed to the enduser in sterile packaging. While at least some drugs presentlycontemplated for use will remain stable during ethylene oxidesterilization, exposure to oxygen during lengthy distribution andstorage periods can adversely affect the drug.

For these reasons, it would be desirable to provide improved methods andsystems for sterilizing and packaging medical devices.

SUMMARY OF THE INVENTION

The present invention is directed to packages of articles such asmedical devices, methods of packaging such articles and is particularlydirected to packaging articles which are labile when exposed to ambientoxygen concentrations or oxygen containing materials over prolongedperiods of time. The present invention provides convenient, effective,and economical approaches for such packaging. The method of packaging,the packages and the packaging systems are particularly suitable fordrug-device combinations, such as drug-eluting stents and otherdrug-coated medical articles. The packaging, the system and method maybe utilized for sterilizing articles such as medical devices which arereactive to an ambient environment.

The sterilized packaging embodying features of the invention generallyincludes a container which has a wall defining at least part of aninterior configured to receive one or more articles or products forsterilization. The container has a portion, such as part of a wallforming the container, which is permeable to sterilizing gas, e.g. EtO,ethylene oxide with nitrogen, various blends of ethylene oxide andcarbon dioxide, ethylene oxide with chlorofluorocarbon diluent(s),Oxyfume 2000 series of sterilant (from Honeywell Chemicals, Morristown,N.J.), ozone, hydrogen peroxide, chlorine dioxide, or others. Thepermeable portion allows the article or articles to be placed in theinterior, the container sealed, a vacuum applied to the containerinterior and an environment of sterilizing gas in contact with thepermeable portion of the container under conditions which drives thesterilizing gas through the gas permeable portion into the inner chamberto sterilize the one or more products disposed within the chamber.

The container interior is evacuated to about 15 psia to about 0.1 psiapreferably 7 psia to about 0.5 psia for the purpose of aspirating thesterilizing gas through the permeable portion of the container. Duringthis time, the container interior can be partially or totally evacuatedof oxygen and replaced totally or partially with a non-reactive gas suchas nitrogen. This is followed by a steam injection slightly increasingthe vacuum to about 0.1 psia to about 5 psia higher than the containerinterior, preferably to about 1 psia to about 3 psia higher than thecontainer interior. Sterilizing gas maintained about the exterior of thepermeable portion of the container is drawn into the container interiorthrough the permeable portion thereof. The pressure of the sterilizinggas within the container interior for effective sterilization is about20 psia to about 2 psia, preferably about 15 psia to about 5 psia. Thedwell time of the sterilizing gas within the container interior at thatpressure is about 1 to about 24 hours preferably about 6 to about 18hours.

After the sterilization, essentially all of the sterilizing gas isremoved from the container interior, either by exposing the interior toa vacuum, by flushing or purging the container interior with air or anon reactive gas such as nitrogen, or some combination thereof or both.Usually, after the sterilizing gas is removed from the containerinterior, the sterilized package is left at room temperature for severaldays to ensure that the interior is essentially free of sterilizing gas,i.e. less than about 150 ppm, preferably about 10 to about 50 ppm, andtypically about 25 ppm.

At this point, at least the permeable portion of the container is sealedto prevent permeation of undesirable gas into the container interiorwhile the one or more articles remain within the interior. The sealingof the container may comprise, for example, sealing the permeableportion of the container with a impermeable patch or partitioning thecontainer to isolate or seal off the portion of the container interiorwhich contains the article(s) from the portion of the container interiorin fluid communication with the gas permeable portion of the container.Optionally, the gas permeable portion of the container may be separated,e.g. severed, from the non-gas permeable portion. Another approach is toplace the sterilized container inside a impermeable enclosure in orderto prevent subsequent gas permeation into the container interiorcontaining the sterilized article(s) through the permeable portion ofthe container. In the latter instance, any atmosphere within theimpermeable enclosure would have to be non-detrimental to the articlesdisposed in the interior of the container within the enclosure. It wouldof course also be possible to combine two or more of these approaches,although that will usually not be necessary.

The gas permeable portion of the container will typically be composed ofa material which is permeable to the sterilizing gas and impermeable toliquids. Suitable gas permeable materials include high-densitypolyethylene (HDPE), typically a spun HDPE or other spun olefin.Commercially available materials such as Tyvek® (2FS, 1059B, 1073B orothers) are specifically designed for packaging medical devices.Typically, the available materials are coated partially or totally withan adhesive for the purpose of sealing the material to itself or toadjacent materials.

The permeability required for the sterilizing gas to permeate into theinterior of the container and contact the one or more articles therein,can vary depending upon the pressure differential, the temperature andthe time available for permeation of the sterilizing gas into theinterior.

In one embodiment, the container has both a gas permeable portion, asdescribed above, and a gas impermeable portion, typically formed from ametal or polymer film or a metal-polymer composite which is impermeableto gases. By “impermeable to gases,” it is meant that the permeation ofoxygen is below about 30 cm³/100 in²/day-atm, preferably below about 2cm³/100 in²/day-atm. Exemplary suitable material for the gas impermeableportion include metal foils such as aluminum; polymer films such aspolyethylene, polyester, polyester (PET)/modified low densitypolyethylene (LDPE) laminated film; or any combination thereof (e.g.,metalized PET).

In one embodiment, the impermeable portions of the container may beincorporated with suitable oxygen scavenger materials or have adjacentthereto a partial or complete film of suitable oxygen absorbers orscavengers, such as ethylene-cyclohexenylmethyl acrylate copolymer(ECHA) and ethylene-methylacrylate-cyclohexeneylmethyl acrylateterpolymer (EMCM) described in Ching et al. (2001), referenced above.Other oxygen scavengers include ethylenically unsaturated polymer,ferrous oxide (partially oxygenated iron), titanium oxide, activatedcarbon with sodium ascorbate, diethylhydroxylamine (DEHA),carbohydrazide, combination of above, or other chemicals which arereadily reactive or combine with oxygen gas. When suitable oxygenscavenger materials are incorporated or lie adjacent to the impermeableportion, oxygen within the interior of the container can be removed tovery low levels. Suitable oxygen levels in the container interior inmost instances will be below 5% oxygen, preferably below 1%, morepreferably below 0.1%.

The permeable portion or portions of the container may be incorporatedwith suitable oxygen scavenger materials or may be positioned adjacentto a partial or complete film of suitable oxygen scavengers. Not onlyoxygen is removed from the package, oxygen gas trying to permeatethrough the permeable portion will be limited from entering the package.

Oxygen scavengers can be placed inside the package, such as inside apermeable packet that is placed within the interior of the container orwithin the interior of an enclosure surrounding the container. Oxygenscavengers can be embedded in a protective sheath over or adjacent tothe article within the inner chamber. The sheath can be a polymerincorporated with suitable oxygen scavenger, or it can be formed of apolymer fully or partially coated with a suitable oxygen scavenger, orit can be made from suitable oxygen scavenger.

Another approach for sealing the gas permeable enclosure is to place apatch, cover, or other gas impermeable barrier over that portion of theenclosure which is initially gas permeable. For example, a window orother area of the enclosure, typically a portion of a pouch, may beformed from gas permeable Tyvek or other material, while the remainingportion of the pouch or other enclosure is formed from a gas impermeablefoil, polymer, or other material. A patch sized to cover the gaspermeable window may be provided to be sealed over the window after theinitial sterilization has been completed.

Another approach for sealing the gas permeable enclosure is to place theenclosure inside of a separate gas impermeable enclosure after theinitial sterilization has been performed.

Preferred gas impermeable materials will also be non-transmissive forlight, UV radiation, heat, and the like. The gas impermeable materialswill also be impermeable to moisture.

In some cases, it will be further desirable to provide desiccantmaterials in or over a portion of the impermeable enclosure in order tosequester any moisture which may remain within the pouch after finalsealing. The desiccant may be coated over or laminated within thepolymer or metal film which comprises the gas impermeable enclosure.Alternatively, a small inserter canister of the desiccant material maybe provided within the enclosure, similar to the desiccant placed inconventional pharmaceutical packaging.

These and other advantages of the invention will become more apparentfrom the following detailed description of the invention when taken inconjunction with the accompanying exemplary drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically illustrates a container embodying features of thepresent invention which includes both gas permeable and gas impermeableportions.

FIG. 2 schematically illustrates an alternate design of a containerembodying features of the present invention which includes a gasimpermeable portions, a gas permeable portion or window and a separateimpermeable patch or cover for sealing the window.

FIG. 3 schematically illustrates an alternate design of a containerhaving features of the present invention which includes gas permeableportions and a gas impermeable outer pouch or enclosure to seal thecontainer.

FIGS. 4A-4E schematically illustrate use of the container shown in FIG.1 for packaging and sterilizing an article in a manner embodyingfeatures of the present invention.

FIG. 5 schematically illustrates one embodiment of the containerconstructed with an impermeable portion having a film adjacent thereto,the film comprising oxygen absorber or scavenger (in pure, composite, ormatrix form).

FIGS. 6A-6C schematically illustrate use of one embodiment of acontainer constructed with a permeable portion incorporated with or hasa film adjacent to made from oxygen scavenger material.

FIG. 7 schematically illustrates use of one embodiment of a containerwith an oxygen scavenger packet or material.

FIG. 8 schematically illustrates use of one embodiment of a containerwith a sheath made from oxygen scavenger material.

FIG. 9 schematically illustrates use of one embodiment of a containerwithin another enclosure that also contains oxygen scavenger material.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Referring now to FIG. 1, a container 10 embodying features of theinvention has a portion 12 which is not permeable to gas and a portion14 which is permeable to gas, particularly to sterilizing gas such asEtO, ethylene oxide with nitrogen, various blends of ethylene oxide andcarbon dioxide, ethylene oxide with chlorofluorocarbon diluent(s),Oxyfume 2000 series of sterilant, ozone, hydrogen peroxide gas plasma,chlorine dioxide, or others. The container 10 typically has an open end16 disposed at one end of the impermeable portion, while the permeableportion 14 is formed about another end of the portion 12. As will bedescribed further with reference to FIGS. 4A-4E below, the container 10is utilized by placing the article to be sterilized into the containerinterior 18 through the open end 16, sealing the open end 16, so thatthe article is fully contained within the gas permeable but otherwiseimpermeable structure of the container prior to sterilization.

An alternative container 20 is depicted in FIG. 2 which has animpermeable portion 22 having a opening 24 covered by a gas permeablelayer or wall 25. The article to be sterilized and packaged may beplaced through open-end 26 of the container 20 into the containerinterior 27 prior to the sealing of the open end. The open end 26 sealedand then sterilization performed by evacuating the interior 27 whilemaintaining a sterilizing gas at the gas permeable layer 25. Aftersterilization, a impermeable sealing patch 28 is placed over the opening24 as indicated by the dotted lines in order to seal the gas permeablelayer 25 against subsequent gas permeation.

FIG. 3, illustrates a third exemplary system 30 for sterilizing andpackaging articles according to the present invention. The system 30includes an inner container 32, at least a portion of which is formedfrom a gas permeable material, and an outer enclosure or pouch 34 whichis at least substantially formed from a gas impermeable material. Theone or more articles to be packaged and sterilized are placed within theinterior of container 32 through the open end 33, the open end 33sealed, and the sealed container sterilized using a sterilizing gaswhich passes through the permeable portion of the container. Residualsterilizing gas within the pouch may be removed as previously described.After the sterilization is complete, the container 32 may be placed intothe open end 36 of the outer enclosure 34, and the open end 36 sealed inorder to prevent subsequent gas permeation into the interior of theouter enclosure 34 and ultimately into the interior of the container 32.

FIGS. 4A-4E illustrate the use of the container 10 for packaging andsterilizing a catheter 40 which carries a drug eluting stent 42 (or anyother environmentally sensitive medical or non-medical article). Thecatheter 40 is first placed through the open end 16 of the container 10so that it is positioned within the interior 18 thereof. The container10 is open at this point so that the gas impermeable portion 12generally surrounds the catheter 40 and the gas permeable portion 14 isdisposed to one side of the catheter, as shown in FIG. 4A.

Open end 16 is sealed, typically by heat sealing, adhesive sealing,lamination, or the like, along a sealing line 44, as shown in FIG. 4B,and the EtO is introduced through the gas permeable portion 14,typically by placing the sealed container 10 within a conventional gassterilizer. Other conditions of sterilization will be chosen to becompatible with the nature of the device and/or drug or otherpotentially labile component on the device. After the sterilization iscomplete, the EtO will be removed from the interior of container,typically by vacuum and/or by purging with air, nitrogen, or otherinactive gas. Optionally, as discussed above, a desiccant may be placedwithin the interior of the container and/or a portion of the container,typically the impermeable portion, may contain or be formed of alaminated or otherwise coupled oxygen absorbers or scavenger and/ormoisture desiccants.

As shown in FIG. 4C, after the sterilizing gas has been removed from theinterior 18 of the container 10, the container may be flattened so thatthe catheter 40 remains in the impermeable portion 12, which is isolatedfrom the permeable portion 14 along a partition line 46. The partitionline 46 may then be flattened and sealed, as shown in FIG. 4D, byconventional methods including heat sealing, adhesive bonding,ultrasonic welding, and the like. Preferably, the permeable portion 14is then severed from the impermeable portion 12, as shown in FIG. 4E.The impermeable portion 12 is then ready for transportation and storageprior to use. The impermeable portion 12 itself may be placed in furtherpackaging, such as boxes, trays, or the like.

Referring to FIG. 5, the impermeable portion 12 of the container 10 canbe made from a material with oxygen absorbers or scavengers incorporatedtherein as well as being coated, including lamination or layer 48partially or completely with suitable oxygen absorbers or scavengers.The presence of the oxygen absorbers or scavengers can remove oxygen gasas it permeates into the container interior 18 containing the sterilizedarticles (not shown) during processing and during storage.

Referring to FIGS. 6A, 6B, and 6C, the permeable portion 14 of container10 can be made from a material incorporated with oxygen absorbers orscavengers 50 as well as being coated partially or fully on the interioror exterior surface with a layer (or matrix of oxygen absorbers,scavenger, and/or permeable polymers) 50 or 52 of suitable oxygenabsorbers or scavengers. The presence of the oxygen absorbers orscavengers can remove oxygen gas within the interior 18 as the gaspermeates into the interior during sterilization and during storage.Even if the permeable portion of the enclosure is not eliminated fromthe path between outside and the drug device, oxygen can be limited fromentering the interior 18.

Referring to FIG. 7, the container 10 contains oxygen absorbers orscavengers within the interior 18 that may be packaged in its own packet54 made from oxygen permeable material such as silicone rubber,polystyrene or any polymer that has an oxygen permeability coefficientgreater than about 30 cm³/100 in²/day-atm, matrix into a oxygenpermeable polymer, or in its original form with or without a oxygenpermeable coating. The oxygen absorbers or scavengers inside the packet54 absorbs any oxygen gas that may enter the interior 18 duringsterilization and storage.

Referring to FIG. 8, the container 10 contains a protective sheath 56made from suitable oxygen absorbers or scavengers that is adjacent tothe drug coated device 58. The sheath 56 can be made directly fromsuitable oxygen absorbers or scavengers such as ferrous oxide orethylene-cyclohexenylmethyl acrylate copolymer, or an oxygen permeablepolymer matrix with the oxygen absorber or scavenger. The protectivesheath oxygen absorbers or scavengers inside the enclosure and adjacentto the drug device will locally absorb any oxygen gas that may enter theinner chamber of the container 10 during sterilization and storage andminimize oxygen gas in the vicinity of the drug device.

FIG. 9 illustrates container 10 that is similar to the container shownin FIGS. 5 and 6 or has oxygen absorbers or scavengers similar to thatshown in FIG. 7. The container 10 is disposed within the interior of anouter enclosure 34. Oxygen absorbers or scavengers are provided in theouter enclosure such as in a packet 60 as shown to reduce the oxygenlevel within the enclosure 34 to prevent penetration into the interior18 of the container 10. Moreover, such scavengers can reduce the oxygenlevel within the interior 18 through the permeable portion of thecontainer since oxygen is freely transported through the permeableportion of the container and that the scavengers attract the oxygen gas.Optionally, desiccants may be placed inside the interior of the outerand/or containers to reduce, maintain and/or control the moisturecontent of the container.

The present invention relies upon gas sterilization where the articlesto be sterilized are first placed and sealed within a container. Atleast a portion of the container is gas permeable so that one or morearticles within the interior of the container may be sterilized byplacing the container in an environment of the sterilizing gas,typically an environment of essentially all ethylene oxide. Once the oneor more articles are placed in the interior of the container, theinterior may be evacuated to remove ambient gases which may be present.Sterilizing gas is introduced into the container interior through thepermeable portion of the container and maintained within the containerinterior at sufficient levels to sterilize the articles therein. Aftersterilization is complete, the interior is preferably evacuated toremove the sterilizing gas, and the container is modified, partitioned,replaced into a secondary enclosure, or otherwise placed in a conditionso that further gas exchange between the exterior and interior of thecontainer is inhibited or prevented. The method and system of thepresent invention provide for convenient and effective sterilization ofarticles using a conventional gas sterilant, and prevent the degradationof the sterilized articles or portions thereof by subsequent exposure tooxygen, water, or other ambient gases.

EtO sterilization and packaging according to the present inventionusually employs five major steps, including: pre-sterilizationconditioning, sterilization, evacuation, air wash, and aeration. Theconditioning step includes placing the one or more articles to besterilized into the interior of the container, sealing the container andevacuating the gas from the container interior. The sterilization stepincludes introducing the sterilant into the interior of the container bypassing a sterilizing gas through the permeable portion of thecontainer, establishing the appropriate operating parameters, such astemperature, pressure, and relative humidity, within the inner chamberand keeping these conditions in the chamber for a pre-determined periodof time for effective sterilization of the articles. The container maybe placed in a sterilization vessel with the atmosphere surrounding thecontainer within the vessel being adjusted to control the procedure. Theevacuation step after sterilization includes the removal of EtO from thecontainer interior by one or more vacuum washes and/or one or morepurges with air or nitrogen, or combinations thereof. In order tofurther remove residual EtO from the inner chamber, the containerpackage then undergoes aeration which can be performed in either thesterilization vessel or in a separate aeration chamber.

The EtO sterilization process embodying features of the presentinvention is performed at process parameters which are particularlyuseful and effective in the sterilization of an article which is atleast in part formed of a reactive or labile material, such as atherapeutic agent coated on the device, while minimizing adverse effectson the integrity of the reactive or labile material during and poststerilization process. The packaged device sterilized according to thepresent invention enables enhanced product shelf-life and greaterconfidence in the integrity and suitability of the sterilized ageddevice.

The sterilization step is preferably carried out at a temperature below30° C. with a dwell time of about 6 to 18 hours or greater. Whileethylene oxide is reactive in both liquid and gaseous phase, it ispreferred to employ EtO in gaseous phase to increase penetration of thegas into the device/package and its reactivity. Either or both, highertemperature and lower pressure as well as relative humidity can increasegas penetration and/or reactivity.

The boiling point for ethylene oxide at atmospheric pressure is about10° C. (51° F.) where EtO is in gaseous state. Therefore, thistemperature of 1° C. is the preferred lowest temperature at which toperform the sterilization step at atmospheric pressure. Alternatively,the temperature of the container interior can further be reduced below10° C. by further reducing the pressure to below atmospheric pressure.By way of example, the sterilization step can effectively be performedat a temperature of 0° C. by reducing the pressure within the containerinterior to about 4 psi (pounds per square inch).

The following examples are offered by way of illustration, not by way oflimitation.

EXAMPLE 1

A drug eluting stent mounted onto the balloon of a stent deliverycatheter (a drug eluting stent system) is packaged in a foil pouch thathas a permeable portion or patch formed of Tyvek®. The pouch issubjected to a vacuum within the inner chamber with a surroundingatmosphere of EtO gas at temperatures of 60° C. to sterilize the drugeluting stent and delivery catheter. After sterilization, the pouch isresealed with the stent and delivery system within the post seal areaand the Tyvek patch outside the post-seal area. The foil pouch minimizesthe light exposure as well the oxygen and moisture exposure to thesterilized contents of the container.

EXAMPLE 2

A drug eluting stent mounted onto the balloon of a stent deliverycatheter is packaged in a Tyvek pouch along with ferrous oxide as anoxygen absorber and desiccant. The pouch is closed, subjected toethylene oxide gas which permeates the pouch. After sterilization, theTyvek pouch is evacuated and purged with nitrogen and air to removeessentially all EtO and then placed inside a gas impermeable foil pouch.The foil pouch is evacuated by vacuum to remove the remaining air andnitrogen gas, and then finally sealed. The foil pouch minimizes theexposure of the sterilized product within the Tyvek pouch to light andto oxygen and moisture, thus providing a long shelf life.

EXAMPLE 3

A drug eluting stent crimped onto a PTCA catheter or a drug elutingstent system is packaged on Tyvek pouch along with ferrous oxide oxygenabsorbers and desiccant. The pouch is sterilized by ethylene oxide gaswith sterilization temperatures of about 55° C. After sterilization, thesterilized Tyvek pouch with the stent system sealed inside is insertedinside a foil pouch. The foil pouch is sealed using a vacuum sealer thatfirst purge the bag with nitrogen gas which replaces the air inside thefoil pouch and that finally seal the foil pouch. This minimizes thelight exposure as well as limit oxygen and moisture exposure.

EXAMPLE 4

A drug eluting stent mounted onto the balloon of a stent deliverycatheter is packaged in an essentially gas impermeable foil containerthat has a Tyvek patch which allows for gas permeability through the gaspermeable patch. The pouch is exposed to ethylene oxide gas using thefollowing cycle: Set Point Chamber Temperature 77° F. (25° C.)Preconditioning Time 3 hrs Initial Evacuation Pressure 1 psia EtO DwellPressure 7 psia EtO Exposure Time 14 hrs Number of Air Wash after 12times sterilization Air Wash Time 10 hrs Room Temperature (20° C.) 3days Aeration

EXAMPLE 5

A drug eluting stent mounted onto the balloon of a stent deliverycatheter is packaged on foil pouch that has a Tyvek patch (i.e.,breathable). The pouch is exposed to ethylene oxide gas using thefollowing cycle: Set Point Chamber Temperature 84° F. (29° C.)Preconditioning Time 3 hrs Initial Evacuation Pressure 1 psia EtO DwellPressure 7 psia EtO Exposure Time 14 hrs Number of Air Washes 12 timesAir Wash Time 10 hrs Room Temperature (20° C.) 3 days Aeration

EXAMPLE 6

A drug eluting stent is crimped onto the balloon of a stent deliverycatheter. A protective sheath made from ethylene-cyclohexenylmethylacrylate copolymer (an oxygen absorber) is inserted over the drugeluting device. The drug eluting stent and delivery catheter is packagedin a Tyvek pouch, the pouch is sealed and then sterilized by ethyleneoxide gas at normal sterilization parameters. The protective sheathformed of oxygen absorbing polymer material minimizes the oxidativedegradation of the drug eluting stent by limiting exposure to oxygengas.

While the invention has been described herein primarily in terms ofpackaging medical devices, and in particular to drug eluting stents, itis also suitable for sterilization and packaging of other articles,including foods, pharmaceuticals, diagnostic and assay systems,sensitive electrical components, chemical system components, and thelike, where the ability to sterilize articles after initial packaginghas been completed is desirable. The methods and systems of the presentinvention are simple to perform, require minimum changes from existingpackaging practices, and provide a package to the end user which is asconvenient and easy to use as prior packaging systems.

Many other alterations and modifications may be made by those ofordinary skill in this art, without departing from the spirit and scopeof this invention. For example, the method and packaging may be utilizedfor packaging articles treated by gases other than sterilizing gases Theillustrated embodiments have been shown only for purposes of clarity andthe examples should not be taken as limiting the invention as defined inthe following claims. The claims are intended to include allequivalents, whether now or later devised.

Moreover, individual features of embodiments of the invention may beshown in some drawings and not in others, but those skilled in the artwill recognize that individual features of one embodiment of theinvention can be combined with one or more features of anotherembodiment. Accordingly, it is not intended that the invention belimited to the specific embodiments illustrated or described. It istherefore intended that this invention to be defined by the scope of theappended claims as broadly as the prior art will permit.

Terms such a “element,” “member,” “component,” “device,” “section,”“portion,” “means,” “steps” and words of similar import when used hereinshall not be construed as invoking the provisions of 35 U.S.C. §112(6)unless the following claims expressly use the term “means” followed by aparticular function without specific structure or expressly use the term“step” followed by a particular function without specific action. Allpatents and patent applications referred to above are herebyincorporated by reference in their entirety.

1. A method for packaging a sterile article, comprising: a. providing acontainer which has a wall defining at least in part an interior andwhich has at least one portion permeable to sterilizing gas; b. placingan article into the interior of the container; c. exposing at least onepermeable portion of the container to an exterior environment whichincludes a sterilizing gas under conditions such that the sterilizinggas permeates through at least one permeable portion of the containerinto the interior of the container; and d. removing sterilizing gas fromthe interior of the container after the articles therein are sterilized.2. The method of claim 1 wherein the at least one permeable region ofthe container is sealed after the sterilizing gas is removed from theinterior to prevent gas permeation while the article remains in theinterior.
 3. A method as in claim 1, wherein the sterilizing gas is atleast in part ethylene oxide.
 4. A method as in claim 1, wherein thesterilizing gas is removed from the interior of the container byapplying a vacuum to the interior.
 5. A method as in claim 1, whereinthe sterilized gas is removed from the interior of the container bypurging the interior of the container with a non-active gas.
 6. A methodas in claim 1, wherein sealing comprises partitioning the container toisolate the article within an impermeable portion of the containerinterior.
 7. A method as in claim 6, further comprising removing the gaspermeable portion of the container.
 8. A method as in claim 1, whereinsealing comprises deploying the container into an impermeable enclosure.9. A method as in claim 1, wherein the container is sealed by applying agas impermeable barrier over the gas permeable portion of the container.10. A method as in claim 1, wherein the article within the interior ofthe container is a medical device.
 11. A method as in claim 10, whereinthe medical device is formed at least in part of a labile material whichis degradable in an atmosphere containing oxygen and/or water vapor. 12.A method as in claim 10, wherein the medical device is a stent coatedwith a therapeutic or diagnostic agent.
 13. A method as in claim 12wherein the interior of the container has less than about 150 ppmsterilizing gas or residuals.
 14. A method as in claim 12 wherein thecontainer interior has about 10 ppm to about 50 ppm sterilizing gas orresiduals.
 15. A method as in claim 1 wherein the sterilizing gas isselected from the group consisting of ethylene oxide, ethylene oxide andnitrogen, ethylene oxide and carbon dioxide, ethylene oxide with one ormore chlorofluorocarbon diluents, Oxyfume 2000 series of sterilant,ozone, hydrogen peroxide gas plasma, chlorine dioxide and mixturesthereof.
 16. A sterile packaging system for one or more sterilearticles, comprising: a. a container which has a wall, an interiordefined at least in part by the container wall and configured to receiveat least one article and at least one portion that is permeable tosterilizing gas and is in fluid communication with the interior, and b.a patch of impermeable material on the permeable portions to preventpermeation of gas into the interior through the permeable portions. 17.The sterile packaging system as in claim 16 wherein the containerinterior is essentially free of sterilizing gas.
 18. The sterilepackaging system as in claim 16 wherein the container interior has lessthan about 150 ppm sterilizing gas or residuals.
 19. The sterilepackaging system as in claim 16 wherein the sterilizing gas is selectedfrom the group consisting of ethylene oxide, ethylene oxide andnitrogen, ethylene oxide and carbon dioxide, ethylene oxide with one ormore chlorofluorocarbon diluents, Oxyfume 2000 series of sterilant,ozone, hydrogen peroxide gas plasma, chlorine dioxide and mixturesthereof.
 20. A system as in claim 16, wherein the at least one gaspermeable portion is formed of material which is impermeable to liquid.21. A system as in claim 16, wherein the at least one gas permeableportion is at least in part formed of a spun olefin.
 22. A system as inclaim 16, wherein the patch sealing the permeable portion is formed of amaterial which is moisture and gas impermeable and is non-transmissivefor light and UV radiation.
 23. A system as in claim 16, wherein thesealing patch is part of a gas impermeable enclosure which receives thecontainer.
 24. The system of claim 23 wherein the impermeable enclosureis sealed about the container to isolate the container from anatmosphere containing oxygen and moisture.
 25. A system as in claim 23,wherein the enclosure is formed of a polymer film which is impermeableto oxygen and moisture.
 26. A system as in claim 16, wherein thecontainer has a first portion which is impermeable to gas and a secondportion which is permeable to gas, and wherein the first portionimpermeable to gas contains the one or more articles and the secondportion permeable to gas is sealed from the first portion by a partitionline which can be selectively adhered to isolate the portion of theinterior of the container within the gas impermeable portion from theinner portion of the gas permeable portion.
 27. A system as in claim 16,wherein the enclosure receiving the container is a pouch having asealable open end and a receptacle portion formed from a non-gaspermeable material and wherein the gas permeable portion lies betweenthe receptacle portion and the open end and a partition line liesbetween the gas permeable portion and the receptacle portion.
 28. Thesystem of claim 16 wherein the container has oxygen absorbers orscavengers.
 29. The system of claim 28 wherein oxygen absorbers orscavengers are provided in fluid communication with the interior of thecontainer.
 30. The system of claim 28 wherein the oxygen absorbers orscavengers are inside the permeable portion of the container.
 31. Thesystem of claim 28 wherein an oxygen absorber is incorporated into orcoated on the permeable portion of the container.
 32. The system ofclaim 28 wherein an oxygen absorber is incorporated into or coated onthe impermeable portion of the container.
 33. The system of claim 28wherein the oxygen absorber is coated onto an interior surface of thecontainer.
 34. The system of claim 28 wherein the oxygen absorber iscoated onto an exterior surface of the container.
 35. The system ofclaim 28 wherein the oxygen absorber is selected from the groupconsisting of ethylene-cyclohexenylmethyl acrylate copolymer andethylene-methylacrylate-cyclohexeneylmethyl acrylate terpolymer.
 36. Thesystem of claim 28 wherein the oxygen scavenger is selected from thegroup of materials consisting of ethylenically unsaturated polymers,ferrous oxide, titanium oxide, activated carbon with sodium ascorbate,diethylhydroxylamine, carbohydrazide, combinations of these materials.37. The system of claim 28 wherein the oxygen absorbers or scavengersare packaged in a packet made from oxygen permeable material that has anoxygen permeability coefficient greater than 30 cm³/100 in²/day-atm. 38.The system of claim 28 wherein the oxygen absorbers or scavengers arepackaged in a packet made from oxygen permeable material that has anoxygen Permeability Coefficient greater than 100 cm³/100 in²/day-atm.39. The system of claim 28 wherein the oxygen absorbers or scavengersare packaged in a packet made from oxygen permeable material that has anoxygen permeability coefficient greater than about 300 cm³/100in²/day-atm.
 40. The system of claim 28 wherein the oxygen absorbers orscavengers are incorporated into a protective sheath that is disposedproximate to the sterilized medical device.
 41. A sterilized package,comprising: a. a sealed container which has an interior defined at leastin part by a wall, which has at least a portion permeable to sterilizinggas and which has at least one sterilized article within the interior;and b. an atmosphere within the interior of the container which issubstantially free of sterilizing gas.
 42. The sterilized package ofclaim 41 wherein the container portion permeable to sterilizing gas issealed to prevent penetration of non-sterilizing gas exterior to thecontainer into the interior of the container.
 43. The sterilized packageof claim 41 wherein an oxygen scavenger is maintained in fluidcommunication with the interior of the container.
 44. The sterilizedpackage of claim 43 wherein the oxygen scavenger is in particulate form.45. The sterilized package of claim 43 wherein the oxygen scavenger isincorporated within at least part of a wall defining the interior of thecontainer.
 46. The sterilized package of claim 41 wherein the containeris sealed by disposing the container in a gas impermeable enclosure. 47.The sterilized package of claim 46 wherein the gas impermeable enclosureis formed at least in part of a polymer which is impermeable to vaporand moisture.
 48. The sterilized package of claim 41 wherein the atleast one article is a drug eluting stent.
 49. The sterilized package ofclaim 48 wherein the stent is coated with a drug that is degraded byoxygen and/or water vapor.
 50. The sterilized package of claim 48wherein the stent is mounted on a balloon of a delivery catheter. 51.The sterilized package of claim 41 wherein the atmosphere within thecontainer interior has less than about 150 ppm sterilizing gas orresiduals.
 52. A method of packaging and treating an article,comprising: a. providing a container which has an interior defined atleast in part by a wall, which has a portion permeable to treating gasand which has a article to be treated disposed within the interior ofthe container; b. surrounding the permeable portion of the containerwith a treating gas under conditions which facilitate permeation of thetreating gas through the permeable portion of the container into thecontainer interior to treat the article disposed therein; and c.removing treating gas from the inner chamber after the article has beentreated.
 53. The method of claim 52 wherein treating gas is removed fromthe interior of the container by purging the interior with innocuousgas.
 54. The method of claim 53 wherein the container interior is purgedwith innocuous gas until substantially free of treating gas.
 55. Themethod of claim 53 wherein the container interior has less than about150 ppm treating gas or residuals.
 56. The method of claim 54 whereinthe permeable portion is sealed after the container interior is purgedwith innocuous gas.
 57. The method of claim 52 wherein the article is amedical device.
 58. The method of claim 57 wherein the medical device isa delivery catheter with an inflatable balloon and a drug eluting stentmounted on the balloon.
 59. The method of packaging and sterilizing amedical device as in claim 52 wherein the sterilizing gas is removedfrom the container interior until essentially free of sterilizing gas.60. The method of packaging and sterilizing a medical device as in claim52 wherein the sterilizing gas is removed from the container interioruntil the interior has less than about 150 ppm sterilizing gas orresiduals.
 61. A method of packaging and sterilizing a medical device asin claim 52 wherein the sterilizing gas is selected from the groupconsisting of ethylene oxide, ethylene oxide and nitrogen, ethyleneoxide and carbon dioxide, ethylene oxide with one or morechlorofluorocarbon diluents, Oxyfume 2000 series of sterilant, ozone,hydrogen peroxide gas plasma, chlorine dioxide and mixtures thereof. 62.A treated package, comprising: a. a sealed container which has aninterior defined at least in part by a wall, which has at least aportion permeable to treating gas and which has at least one treatedarticle within the interior; and b. an atmosphere within the interior ofthe container which is substantially free of treating gas.
 63. A methodfor packaging one or more treated articles, comprising: a. providing acontainer which has a wall defining at least in part an interior andwhich has at least one portion permeable to treating gas; b. placing oneor more articles into the interior of the container; c. exposing atleast one permeable portion of the container to an exterior environmentwhich includes a treating gas under conditions such that the treatinggas permeates through at least one permeable portion of the containerinto the interior of the container; and d. removing treating gas fromthe interior of the container after the articles therein are treated.64. A packaging system for one or more treated articles, comprising acontainer which has a wall, an interior defined at least in part by thecontainer wall and configured to receive at least one article and atreating gas permeable means in fluid communication with the interior.65. The packaging system of claim 64 wherein a patch of impermeablematerial covers at least part of the permeable means to preventpermeation of gas into the interior.
 66. A method for packaging one ormore treated articles, comprising: a. a step of providing a containerwhich has a wall defining at least in part an interior and which has atleast one portion permeable to treating gas; b. a step of placing one ormore articles into the interior of the container; and c. a step ofexposing at least one permeable portion of the container to an exteriorenvironment which includes a treating gas under conditions such that thetreating gas permeates through at least one permeable portion of thecontainer into the interior of the container.
 67. The method of claim 66including the step of removing treating gas from the interior of thecontainer after the articles therein are treated.